Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDEC1KO)

• DOT Name: TATA box-binding protein-like 2 (TBPL2)
• Synonyms: TBP-like 2; TATA box-binding protein-related factor 3; TBP-related factor 3
• Gene Name: TBPL2
• Related Disease:
  Metabolic disorder
  Neoplasm
  Adult T-cell leukemia/lymphoma
  Arteriosclerosis
  Atherosclerosis
  Bone osteosarcoma
  Cataract
  Colon cancer
  Endometriosis
  Hepatitis C virus infection
  Leiomyoma
  Osteosarcoma
  Retinoblastoma
  T-cell leukaemia
  Type-1/2 diabetes
  Uterine fibroids
  Advanced cancer
  Female hypogonadism
  Hypoglycemia
• UniProt ID: TBPL2_HUMAN
• Pfam ID: PF00352
• Sequence:
  MEQEETYLELYLDQCAAQDGLAPPRSPLFSPVVPYDMYILNASNPDTAFNSNPEVKETSG
  DFSSVDLSFLPDEVTQENKDQPVISKHETEENSESQSPQSRLPSPSEQDVGLGLNSSSLS
  NSHSQLHPGDTDSVQPSPEKPNSDSLSLASITPMTPMTPISECCGIVPQLQNIVSTVNLA
  CKLDLKKIALHAKNAEYNPKRFAAVIMRIREPRTTALIFSSGKMVCTGAKSEEQSRLAAR
  KYARVVQKLGFPARFLDFKIQNMVGSCDVRFPIRLEGLVLTHQQFSSYEPELFPGLIYRM
  VKPRIVLLIFVSGKVVLTGAKERSEIYEAFENIYPILKGFKKA
• Function: Transcription factor required in complex with TAF3 for the differentiation of myoblasts into myocytes. The complex replaces TFIID at specific promoters at an early stage in the differentiation process.
• Tissue Specificity: Ubiquitously expressed in all tissues examined with highest levels in heart, lung, ovary, spleen and testes.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway: Germ layer formation at gastrulation (R-HSA-9754189)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[2]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[5]
Cataract	DISUD7SL	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Endometriosis	DISX1AG8	Strong	Altered Expression	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[9]
Leiomyoma	DISLDDFN	Strong	Biomarker	[10]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[5]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[3]
T-cell leukaemia	DISJ6YIF	Strong	Altered Expression	[3]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[6]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[10]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[6]
Female hypogonadism	DISWASB4	moderate	Biomarker	[11]
Hypoglycemia	DISRCKR7	moderate	Biomarker	[12]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of TATA box-binding protein-like 2 (TBPL2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of TATA box-binding protein-like 2 (TBPL2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of TATA box-binding protein-like 2 (TBPL2).	[16]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of TATA box-binding protein-like 2 (TBPL2).	[14]

References

• [1] Anti-oxidative, anti-cancer and anti-inflammatory actions by thioredoxin 1 and thioredoxin-binding protein-2.Pharmacol Ther. 2010 Sep;127(3):261-70. doi: 10.1016/j.pharmthera.2010.04.004. Epub 2010 May 8.
• [2] Histone deacetylase inhibitor suberoylanilide hydroxamic acid suppresses the pro-oncogenic effects induced by hepatitis B virus pre-S2 mutant oncoprotein and represents a potential chemopreventive agent in high-risk chronic HBV patients.Carcinogenesis. 2013 Feb;34(2):475-85. doi: 10.1093/carcin/bgs365. Epub 2012 Nov 21.
• [3] Loss of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type I-dependent T-cell transformation: implications for adult T-cell leukemia leukemogenesis.Cancer Res. 2004 Feb 15;64(4):1287-92. doi: 10.1158/0008-5472.can-03-0908.
• [4] Thioredoxin and related molecules--from biology to health and disease.Antioxid Redox Signal. 2007 Jan;9(1):25-47. doi: 10.1089/ars.2007.9.25.
• [5] Involvement of ETS1 in thioredoxin-binding protein 2 transcription induced by a synthetic retinoid CD437 in human osteosarcoma cells.Biochem Biophys Res Commun. 2010 Jan 1;391(1):621-6. doi: 10.1016/j.bbrc.2009.11.109. Epub 2009 Nov 20.
• [6] The Function of Thioredoxin-Binding Protein-2 (TBP-2) in Different Diseases.Oxid Med Cell Longev. 2018 May 2;2018:4582130. doi: 10.1155/2018/4582130. eCollection 2018.
• [7] Characterization of the HDAC1 complex that regulates the sensitivity of cancer cells to oxidative stress.Cancer Res. 2009 Apr 15;69(8):3597-604. doi: 10.1158/0008-5472.CAN-08-4368. Epub 2009 Apr 7.
• [8] The roles of thioredoxin and thioredoxin-binding protein-2 in endometriosis.Hum Reprod. 2010 May;25(5):1251-8. doi: 10.1093/humrep/deq027. Epub 2010 Feb 19.
• [9] Expression of thioredoxin and thioredoxin-binding protein-2 in the liver of patients with chronic hepatitis C as a predictor of response to interferon therapy.Int J Mol Med. 2006 Jun;17(6):989-95.
• [10] Comparative expression of thioredoxin-1 in uterine leiomyomas and myometrium.Mol Hum Reprod. 2014 Feb;20(2):148-54. doi: 10.1093/molehr/gat069. Epub 2013 Oct 15.
• [11] TBP2 gene may not be associated with primary ovarian insufficiency.Climacteric. 2016 Dec;19(6):565-567. doi: 10.1080/13697137.2016.1231175. Epub 2016 Sep 17.
• [12] Thioredoxin binding protein-2/thioredoxin-interacting protein is a critical regulator of insulin secretion and peroxisome proliferator-activated receptor function.Endocrinology. 2009 Mar;150(3):1225-34. doi: 10.1210/en.2008-0646. Epub 2008 Oct 30.
• [13] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [14] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.